Citations

Background: The agrammatic variant of primary progressive aphasia (PAA), primary progressive apraxia of speech (PPAOS), or a combination of both (AOS-PAA) are neurodegenerative disorders characterized by speech-language impairments and together compose the AOS-PAA spectrum disorders. These patients typically have an underlying 4-repeat tauopathy, although they sometimes show evidence of amyloid-β and tau deposition on PET, suggesting Alzheimer’s disease (AD). Given the growing number of pharmacologic treatment options for AD, it is important to better understand the incidence of AD pathology in these patients. Objective: This study aimed to evaluate the frequency of amyloid-β and tau positivity in AOS-PAA spectrum disorders. Sixty-five patients with AOS-PAA underwent a clinical speech-language battery and PiB PET and flortaucipir PET imaging. Methods: Global PiB PET standardized uptake value ratios (SUVRs) and flortaucipir PET SUVRs from the temporal meta region of interest were compared between patient groups. For 19 patients who had died and undergone autopsy, their PET and pathology findings were also compared. Results: The results showed that although roughly half of the patients are positive for at least one biomarker, their clinical symptoms and biomarker status were not related, suggesting that AD is not the primary cause of their neurodegeneration. All but one patient in the autopsy subset had a Braak stage of IV or less, despite four being positive on tau PET imaging. Conclusions: Inclusion criteria for clinical trials should specify clinical presentation or adjust the evaluation of such treatments to be specific to disease diagnosis beyond the presence of certain imaging biomarkers.

AbstractBackgroundThe semantic fluency task involves naming as many items as possible in a given category (e.g., animals) in one minute. It is often interpreted as a measure of word retrieval, but also draws on executive function abilities to organize responses and develop task‐specific strategies. Indeed, both language skills and dementia severity ratings have recently been found to correlate with semantic fluency performance in patients with primary progressive aphasia (Riello et al., 2022; Scheffel et al., 2021). Here, we focused instead on how performance on language and executive function measures predicts longitudinal change in semantic fluency performance in patients with progressive agrammatic aphasia and/or apraxia of speech (AOS).MethodPatients with isolated agrammatic aphasia (n = 10), isolated AOS (n = 42), or a combination of the two (n = 59) with 1‐7 visits (mean = 2.19) were included. We used Bayesian hierarchical linear models to investigate whether baseline measures of executive function or language were associated with the rate at which semantic fluency performance changes over time while accounting for baseline diagnosis group, sex, education, age at baseline, and baseline disease duration.ResultSemantic fluency performance declined over time, at a similar rate irrespective of diagnostic group (isolated or combined aphasia or AOS; Figure 1). Across all patients, higher executive function abilities at baseline, as indicated by faster Trails Making Test B completion times, predicted higher baseline semantic fluency performance and also a steeper annual rate of decline (Figure 2). Similarly, higher fluency ratings during the Western Aphasia Battery‐Revised picture description at baseline were associated with higher baseline semantic fluency performance and faster decline. Baseline performance on the Boston Naming Test and Token Test were also associated with baseline semantic fluency, but not with longitudinal change.ConclusionThese results better delineate how language and executive function abilities support performance in the semantic fluency task. Higher abilities in those areas at baseline do not appear to be protective over time. Rather, the differences in semantic fluency that are present at baseline disappear as the disease progresses.

Abstract Posterior cortical atrophy and logopenic progressive aphasia are atypical clinical presentations of Alzheimer’s disease. Resting-state functional connectivity studies have shown functional network disruptions in both phenotypes, particularly involving the language network in logopenic progressive aphasia and the visual network in posterior cortical atrophy. However, little is known about how connectivity differs both within and between brain networks in these atypical Alzheimer’s disease phenotypes. A cohort of 144 patients was recruited by the Neurodegenerative Research Group at Mayo Clinic, Rochester, MN, USA, and underwent structural and resting-state functional MRI. Spatially preprocessed data were analysed to explore the default mode network and the salience, sensorimotor, language, visual and memory networks. The data were analysed at the voxel and network levels. Bayesian hierarchical linear models adjusted for age and sex were used to analyse within- and between-network connectivity. Reduced within-network connectivity was observed in the language network in both phenotypes, with stronger evidence of reductions in logopenic progressive aphasia compared to controls. Only posterior cortical atrophy showed reduced within-network connectivity in the visual network compared to controls. Both phenotypes showed reduced within-network connectivity in the default mode and sensorimotor networks. No significant change was noted in the memory network, but a slight increase in the salience within-network connectivity was seen in both phenotypes compared to controls. Between-network analysis in posterior cortical atrophy showed evidence of reduced visual-to-language network connectivity, with reduced visual-to-salience network connectivity, compared to controls. An increase in visual-to-default mode network connectivity was noted in posterior cortical atrophy compared to controls. Between-network analysis in logopenic progressive aphasia showed evidence of reduced language-to-visual network connectivity and an increase in language-to-salience network connectivity compared to controls. Findings from the voxel-level and network-level analysis were in line with the Bayesian hierarchical linear model analysis, showing reduced connectivity in the dominant network based on diagnosis and more crosstalk between networks in general compared to controls. The atypical Alzheimer’s disease phenotypes were associated with disruptions in connectivity, both within and between brain networks. Phenotype-specific differences in connectivity patterns were noted in the visual network for posterior cortical atrophy and the language network for logopenic progressive aphasia.